Enzyme telomerase

Guyen B et al. (2004) Synthesis and evaluation of analogues of 10H-indolo[3,2-b] quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase. Org Biomol Chem 2(7) 981-988... 

The ends of a linear chromosome are not readily replicated by cellular DNA polymerases. DNA replication requires a template and primer, and beyond the end of a linear DNA molecule no template is available for the pairing of an RNA primer. Without a special mechanism for replicating the ends, chromosomes would be shortened somewhat in each cell generation. The enzyme telomerase solves this problem by adding telomeres to chromosome ends. 

In cells that do not age (for example, germline and cancer cells) the enzyme telomerase replaces the telomeres, thus extending the life of the cell. 

The end of a linear chromosome is called a telomere. Telomeres require a special mechanism, because the ends of a linear chromosome can t be replicated by the standard DNA polymerases. Replication requires both a template and a primer at whose 3 end synthesis begins. The primer can t be copied by the polymerase it primes. What copies the DNA complementary to the primer In a circular chromosome, the primer site is to the 3 direction of another polymerase, but in a linear chromosome, no place exists for that polymerase to bind. As a result, unless a special mechanism for copying the ends of chromosomes is used, there will be a progressive loss of information from the end of the linear chromosome. Two characteristics about telomeres help avoid this situation. First, they consist of a short sequence—for example, AGGGTT—repeated many times at the end of each chromosome. Telomeres, therefore, are part of the highly repetitive DNA complement of a eukaryotic cell. Secondly, a specific enzyme, telomerase, carries out the synthesis of this reiterated DNA. Telomerase contains a small RNA subunit that provides the template for the sequence of the telomeric DNA. Eukaryotic somatic cells have a lifespan of only about 50 doublings, unless they are cancerous. One theory holds that a lack of telomerase in cells outside the germ line causes this limitation. 

Why do eukaryotes contain the enzyme telomerase, while it is absent from E. colil SOLUTION... 

Chromosome duplication in eukaryotic cells requires the enzyme telomerase which replicates the chromosome ends, the telomeres, a task that cannot be carried out by DNA replicases. (Telomerase is a ribonucleoprotein where the RNA moiety serves as template for addition of short nucleotides to the 3 end of the chromosome. The telomerase contains reverse transcriptase motifs which are essential for the duplication of the telomeres. For further information see ref. 20.). The cell-cycle clock is tightly coupled to the telomerase clock. ... 

Telomeres. The ends of linear chromosomes are called telomeres. The enzyme telomerase, an RNA-dependant DNA polymerase that carries its own RNA template, is required for their replication. 

Because DNA polymerases extend their growing polynucleotide chains only in the 5 —> 3 direction, and because the two strands of the parental DNA duplex are antiparallel, removal of the RNA primer that is paired with the 3 end of the parental template DNA would leave an overhanging 3 DNA strand with no means of having its complement synthesized. Ordinary DNA polymerases are unable to initiate DNA chains de novo. Each round of replication would consequently shorten the DNA because a portion could not be copied. To circumvent this problem, human DNA chromosomes have a segment of repeating G-rich DNA (telomeres) at their ends. In addition, a special enzyme, telomerase, which is an RNA-dependent DNA polymerase (reverse transcriptase) that carries its own RNA template, can, in effect, extend the uncompleted end at each round of replication. The RNA template renews the repeating telomere sequence so that the DNA is not shortened (text, pp.765-766). 

Telomeres These occur at the ends of the chromosome and consist of distinct repeated sequences that must be copied before the chromosome can replicate. Special enzymes, telomerases, catalyze the processing of the telomeres. Reduced activity and extent of this processing are implicated in cell aging. 

Telomeres are specialised short DNA sequences that form the ends of linear DNA eukaryotic chromosomes. They contain many copies (-1000 or more) of the short sequence 5-TTAGGG-3 (in humans), and their function is to protect the ends of the chromosomes from degradation. The enzyme telomerase (a ribonucleoprotein complex) is responsible for their synthesis, which is independent of... 

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